Skin Inflammation Activates Intestinal Stromal Fibroblasts and Promotes Colitis

The study investigated the link between skin inflammation and inflammatory bowel diseases (IBDs), revealing that skin inflammation could activate intestinal stromal fibroblasts, promoting their differentiation into preadipocytes with antimicrobial functions. This process was exacerbated by skin injuries and linked to hyaluronan (HA) catabolism, which altered colon fibroblast function and increased colon inflammation. In mouse models, skin injuries worsened colitis, increased disease severity, and delayed recovery, with elevated inflammatory markers in the colon. The study demonstrated that HA fragments from the skin acted as damage-associated molecular patterns (DAMPs), enhancing preadipocyte potential in the colon and increasing susceptibility to colitis. The findings suggested that targeting reactive adipogenesis or immune crosstalk by HA could be a therapeutic approach for IBD, emphasizing the importance of considering skin function in gut health.